In FY 2010, we focused on continued investigation of the staphylococcal peptide cytolysins, phenol-soluble modulins (PSMs). In collaboration with Dr. Andreas Peschels group from the University of Tubingen, Germany, we discovered that the pro-inflammatory effects of PSMs on neutrophils are mediated by binding to the FPR2/ALX receptor. In contrast, cytolytic activities of PSMs are independent of that receptor. Furthermore, we found that several protein synthesis-inhibiting antibiotics, such as tetracycline and clindamycin, trigger increased production of PSMs and of the Agr virulence regulator, which controls PSM production. Current efforts focus on structure-function relationship studies of PSMs and the identification of the PSM exporter, with the long-term goals to produce anti-PSM therapeutics for the treatment of staphylococcal infections. In further work, we continued our efforts to elucidate the basis of virulence in community-associated MRSA strains. In particular, we are investigating the contribution of differential gene expression and production of major toxins to CA-MRSA virulence. These studies are performed in close collaboration with Dr. DeLeos group at RML, Dr. Diep at UCSF, and Dr. Li at Fudan University.